US2929819A - New oxazoles - Google Patents

New oxazoles Download PDF

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Publication number
US2929819A
US2929819A US743018A US74301858A US2929819A US 2929819 A US2929819 A US 2929819A US 743018 A US743018 A US 743018A US 74301858 A US74301858 A US 74301858A US 2929819 A US2929819 A US 2929819A
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United States
Prior art keywords
acid
pyridyl
oxazoles
grams
new
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Expired - Lifetime
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US743018A
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English (en)
Inventor
Erlenmeyer Hans
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CIBA PHARM PROD Inc
CIBA PHARMACEUTICAL PRODUCTS Inc
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CIBA PHARM PROD Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • This invention relates to new oxazoles, more particularly it concerns 2-pyridyl-oxazoles, and their salts.
  • the new oxazoles may contain substituents in both heterocyclic rings, and especially lower alkyl groups, in particular methyl groups.
  • the oxazole radical can be linked to the 2-, 3- or 4-position of the pyridine nucleus.
  • the new compounds possess valuable pharmacological properties. Thus, they have an analgesic action. They are useful as medicaments, and especially as analgesics. Especially valuable is 2-pyridyl-(2')-oxazole of the formula and its salts.
  • the 2-pyridyl-oxazoles can be made by a method in which an a( N- [pyridyl-methylidene] -amino)-aldehydeacetal or -ketone-acetal is subjected to intramolecular condensation under oxidizing conditions.
  • This reaction may be carried out in known manner, advantageously at a raised temperature, in the presence or absence of a diluent and/or a condensing agent, in an open or closed vessel.
  • the new compounds are obtained in the form of the free bases or salts thereof.
  • the free bases may be formed in the usual manner, for example, by treatment with an alkali.
  • therapeutically useful acid addition salts can be made, for example, by reaction with the corresponding acids, for example, hydrohalic acids, sulfuric acid, phosphoric acids, nitric acid, perchloric acid, or aliphatic, aromatic, or heterocyclic carboxylic or sulfonic acids, such as formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, glycollic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, oxymaleic acid, dihydroxymaleic acid, pyroracemic acid; or phenylacetic acid, benzoic acid, para-aminobenzoic acid, anthranilic acid, para-hydroxybenzoic acid, salicylic acid or para-aminosalicylic acid; or me
  • the starting materials are known or can be obtained by methods in themselves known. There are advantageously used those which lead to the formation of the especially valuable 2-pyridyl-oxazole mentioned above.
  • the new oxazoles, and their salts are useful as medicaments, for example, in the form of pharmaceutical prep arations which contain the active compound in admixture with a pharmaceutical organic or inorganic, solid or liquid carrier suitable for enteral, parenteral or topical administration.
  • a pharmaceutical organic or inorganic, solid or liquid carrier suitable for enteral, parenteral or topical administration.
  • the carrier there are used substances which do not react with the new compounds, for example, water, gelatine, lactose, starches, magnesium stearate, talc, vegetable oils, benzyl alcohols, gums, polyalkylene glycols or other known carrier for medicaments.
  • the pharmaceutical preparations may be in the form of tablets, dragees or in liquid form as solutions, suspension or emulsions.
  • auxiliary substances such as preserving, stabilizing, wetting or emulsifying agents, salts for regulating the osmotic pressure or buffers. They may also contain other therapeutically valuable substances.
  • the preparations are made up by the usual methods.
  • Example 1 10 grams of N-[pyridyl-(Z)-methylidene]-amino-acetaldehyde-diethylacetal is slowly introduced dropwise, while stirring, at 0 C. into 42 cc. of concentrated sulfuric acid. The mixture becomes dark yellow in color. While cooling well there are then slowly introduced 17 grams of phosphorus pentoxide. The resulting mixture is heated at 120 C. for 20 minutes. The whole is then allowed to cool and the dark reaction mixture is poured on to about 500 grams of ice. After being neutralized with concentrated aqueous ammonia solution, while cooling, the mixture is treated hot several times with active charcoal and the brownish filtrate is subjected to steam distillation.
  • the distillate is obtained (about 3 liters) is concentrated in vacuo to about 500 cc., then saturated with potassium carbonate, and extracted with ether overnight in a Kutscher-Steudel apparatus.
  • the dried ethereal solution is evaporated and the brownish residual oil is distilled under a high vacuum.
  • There passes over at 70-75 C. under 0.1 mm. pressure a colorless oil which consists of pure 2-pyridyl-(2)-oxazole of the formula This compound forms a monopicrate, which melts at l65-l67 C. after crystallization several times from ethanol.
  • the diethyl acetal used as starting material may be prepared as follows:
  • Example 2 15 grams of N-[6-methyl-pyridyl-(2)-methylidene]- amino-acetaldehyde-diethylacetal are added dropwise at -5 to C. with stirring to 86 cc. of concentrated sulfuric acid. The mixture is added dropwise at to 0 C. with stirring to 36 grams of phosphorus pentoxide and cc. of concentrated sulfuric acid and the whole is heated for 1 hour at 130 C. with stirring. After cooling, the dark brown reaction product is poured on to ice, rendered alkaline with concentrated ammonia and distilled with steam.
  • the distillate (about 2 liters) is acidified with concentrated hydrochloric acid, the solution not being allowed to heat up too much, concentrated under reduced pressure, saturated with potassium carbonate and extracted with either in a Kutseher-Steudel apparatus.
  • the ethereal solution is dried and evaporated.
  • the residue is distilled in a bulb tube at 60 C. under 0.1 mm. pressure of mercury.
  • the resulting 2-[6'-methyl-pyridyl- (2')-l-oxazole of the formula Example 3 5 grams of amino-acetaldehyde-diethylacetal are heated with 4 grams of isonicotinaldehyde for 1 hour at 150 C. The water formed is distilled continuously under reduced pressure.
  • Example 4 By an analogous process using nicotinaldehyde there is obtained the isomeric 2-pyridyl-(3')-oxazole of the formula Example 4
  • the 2-pyridyl-(2')-oxazole described in Example 1 can be worked up in the usual way to a pharmaceutical preparation, for example of the following composition:

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
US743018A 1957-07-11 1958-06-19 New oxazoles Expired - Lifetime US2929819A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH885469X 1957-07-11

Publications (1)

Publication Number Publication Date
US2929819A true US2929819A (en) 1960-03-22

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US743018A Expired - Lifetime US2929819A (en) 1957-07-11 1958-06-19 New oxazoles

Country Status (7)

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US (1) US2929819A (en)van)
BE (1) BE569324A (en)van)
CH (2) CH361281A (en)van)
DE (1) DE1112076B (en)van)
FR (1) FR1200947A (en)van)
GB (1) GB885469A (en)van)
NL (1) NL104788C (en)van)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3036084A (en) * 1958-05-23 1962-05-22 Ciba Ltd New oxazole compounds
US3124587A (en) * 1959-04-04 1964-03-10 Process for the production of pyrtooxal-
US3152135A (en) * 1962-11-02 1964-10-06 Warner Lambert Pharmaceutical Heterocyclic substituted indazole compounds and process therefor
US3244593A (en) * 1963-06-12 1966-04-05 Endo Lab Pharmaceutically active substituted 5-pyrazolones
US3277105A (en) * 1963-12-24 1966-10-04 Ciba Geigy Corp Isoxazoles
US3311655A (en) * 1960-05-24 1967-03-28 France Etat Process for the preparation of urethanes
US3511848A (en) * 1966-03-21 1970-05-12 American Cyanamid Co Certain 4-(isoxazol-3 or 5-yl)-pyridinium salts
US4603422A (en) * 1984-09-26 1986-07-29 The United States Of America As Represented By The Secretary Of The Navy Long-lived laser dye
US9173396B2 (en) 2010-10-22 2015-11-03 Bayer Intellectual Property Gmbh Heterocyclic compounds as pesticides

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1540580A (en) * 1975-09-02 1979-02-14 Shell Int Research Fungicidal isoxazolidines
US4066769A (en) * 1976-12-23 1978-01-03 The Upjohn Company 3,3'-(2,6-pyridinediyl-5-isoxazole carboxylic acids, salts, and esters, compositions and methods of use thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3036084A (en) * 1958-05-23 1962-05-22 Ciba Ltd New oxazole compounds
US3124587A (en) * 1959-04-04 1964-03-10 Process for the production of pyrtooxal-
US3311655A (en) * 1960-05-24 1967-03-28 France Etat Process for the preparation of urethanes
US3152135A (en) * 1962-11-02 1964-10-06 Warner Lambert Pharmaceutical Heterocyclic substituted indazole compounds and process therefor
US3244593A (en) * 1963-06-12 1966-04-05 Endo Lab Pharmaceutically active substituted 5-pyrazolones
US3277105A (en) * 1963-12-24 1966-10-04 Ciba Geigy Corp Isoxazoles
US3511848A (en) * 1966-03-21 1970-05-12 American Cyanamid Co Certain 4-(isoxazol-3 or 5-yl)-pyridinium salts
US4603422A (en) * 1984-09-26 1986-07-29 The United States Of America As Represented By The Secretary Of The Navy Long-lived laser dye
US9173396B2 (en) 2010-10-22 2015-11-03 Bayer Intellectual Property Gmbh Heterocyclic compounds as pesticides

Also Published As

Publication number Publication date
NL104788C (en)van)
FR1200947A (fr) 1959-12-24
GB885469A (en) 1961-12-28
CH361281A (de) 1962-04-15
CH361280A (de) 1962-04-15
BE569324A (en)van)
DE1112076B (de) 1961-08-03

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